The objective of this Program Project is to develop a deeper understanding of the fundamental aspects of protein folding and assembly through an integrated program of experimentation and computation in three dimensional structure analysis. This Program capitalizes on the availability of a Core Facility of state of the art computational, computer graphic, x-ray diffraction and NMR spectroscopy equipment. The research approaches the question of ordering and assembly of structure using both experimental and computational techniques applied to systems that range from peptide fragments to protein complexes. this program builds on a highly successful and productive five years of research which has laid much of the foundation for what is proposed here. In addition, two new projects will expand the breadth of techniques brought to bear on these fundamental problems of structural molecular biology. Dr. Wright in Project VI will use NMR spectroscopy to investigate the formation and stabilization of peptide fragments of proteins. His group will also investigate the coalescence and stabilization of higher order structures that may play a fundamental role in protein folding. In Project V Dr. Wilson will continue and extend his crystallographic studies of antibody antigen complexes in order to experimentally address the questions of peptide and protein flexibility and induced fit in protein complex formation. He will also undertake a new study of the complex formation of IL-2 and its receptor. In Project I Drs. Case and Bashford will develop and apply molecular simulation techniques to aid in the interpretation of experimental results from NMR and infrared spectra of linear peptides. Dr. Skolnick, in project III will apply his successful lattice Monte Carlo techniques to explore pathways of oligomeric protein assembly, large scale domain motion and folding of membrane proteins. In Project II Dr. Olson will extend his work on substrate docking and protein interface formation to encompass larger and more flexible models. He will also use the tools that his group has developed for protein shape analysis to explore protein-protein docking and complex formation. By focusing on overlapping systems, techniques, and questions this Program Project has, and will continue to foster significant collaborative interactions which enhance the value of each individual project.